Severe acute respiratory syndrome (SARS) is a new, potentially life threatening infectious disease of humans. After SARS was first recognized in late February 2003 in Hanoi, Vietnam, the disease spread rapidly, with cases reported from 29 countries on five continents over 4 months (World Health Organization. Severe acute respiratory syndrome (SARS I. Wkly. Epidemiol. Rec. 2003, 78:81-3; Peiris, et al. Coronavirus as a possible cause of severe acute respiratory syndrome. Lancet 2003, 361:1319-25; Lee, et al. A major outbreak of severe acute respiratory syndrome in Hong Kong. N. Eng. J. Med. 2003, 348:1986-94; Tsang, et al. A cluster of cases of severe acute respiratory syndrome in Hong Kong. N. Eng. J. Med. 2003, 348:1977-85; Poutanen, et al. Identification of severe acute respiratory syndrome in Canada. N. Eng. J. Med. 2003, 348:1995-2005; Kuiken, et al. Newly discovered coronavirus as the primary cause of severe acute respiratory syndrome. Lancet 2003, 362:263-70; World Health Organization Multicentre Collaborative Network for Severe Acute Respiratory Syndrome (SARS) Diagnosis. A multicentre collaboration to investigate the cause of severe acute respiratory syndrome. Lancet 2003, 361:1730-3). By Jul. 3, 2003, this epidemic resulted in 8,439 reported cases globally, of which 812 were fatal (Cumulative number of reported probable cases of severe acute respiratory syndrome (SARS). e-publication cited Jul. 8, 2003).
The most common early symptoms of SARS include fever (a measured temperature greater than 100.4° F. (38.0° C.)), chills, headache, myalgia, dizziness, rigors, cough, sore throat, and runny nose (WHO Weekly Epidemiological Record, No. 12, Mar. 21, 2003). The SARS illness usually starts with fever, severe headache, dizziness, and myalgia. After 2 to 7 days, SARS patients generally develop a dry, nonproductive cough. In some cases, there may be rapid deterioration of conditions, with low oxygen saturation and acute respiratory distress.
The SARS-associated coronavirus pathogen was quickly isolated, and its genome has been sequenced by scientists in Canada and the United States (Ksiazek et al., A novel coronavirus associated with severe acute respiratory syndrome. N. Engl. J. Med., Apr. 10, 2003, e-pub; Drosten et al., Identification of a novel coronavirus in patients with severe acute respiratory syndrome. N. Engl. J. Med., Apr. 10, 2003, e-pub; WHO Update 31, Coronavirus never before seen in humans is the cause of SARS, Apr. 16, 2003). Rapid identification of the causal agent as a novel coronavirus (SARS-CoV) represents an extraordinary achievement in the history of global health and helped to contain the epidemic (World Health Organization Multicentre Collaborative Network for Severe Acute Respiratory Syndrome (SARS) Diagnosis. A multicentre collaboration to investigate the cause of severe acute respiratory syndrome. Lancet 2003 361:1730-3). Nonetheless, the epidemiology and pathogenesis of SARS remain poorly understood, and definitive diagnostic tests or specific treatments are not established. Since the origin of the virus and its animal reservoirs remain to be defined, the potential for recurrence is unknown. This fact underscores the importance of establishing sensitive and efficient methods for diagnosis and surveillance.
The coronavirus that has been implicated in SARS represents the prototype of a new lineage of coronaviruses capable of causing outbreaks of clinically significant and frequently fatal human disease. Coronaviruses were first isolated from chicken in 1937, and from human in 1965. The coronavirus family contains approximately 15 species, which infect a broad range of animals, including humans, cats, dogs, cows, pigs, rodents, and birds (e.g., chickens). The coronavirus is a single-stranded, (+)sense RNA virus. The virus enters the host cell via endocytosis, and reproduces itself in the cytoplasm; no DNA stage is involved. New virions form by budding into the Golgi apparatus, being transported to the cell surface, and secreted from host cell.
To date, there is only a limited repertoire of sensitive, specific diagnostic assays available that allow surveillance and clinical management of SARS and SARS-associated diseases. As specific antiviral therapies are established, early diagnosis will be increasingly important in minimizing morbidity and mortality. Immunofluorescence and enzyme-linked immunosorbent assays (ELISA) are reported to inconsistently detect antibodies to SARS-CoV before day 10 or 20 after the onset of symptoms, respectively (World Health Organization Multicentre Collaborative Network for Severe Acute Respiratory Syndrome (SARS) Diagnosis. A multicentre collaboration to investigate the cause of severe acute respiratory syndrome. Lancet 2003, 361:1730-3; Li G Chen X and Xu A. Profile of specific antibodies to the SARS-associated coronavirus. N. Eng. J. Med. 2003, 349:5-6). Thus, although helpful in tracking the course of infection at the population level, these serologic tools have less usefulness in detecting infection at early stages, when there may be potential to implement therapeutic interventions or measures, such as quarantine that may reduce the risk for transmission to naive persons. In contrast, polymerase chain reaction (PCR)-based assays have the potential to detect SARS and SARS-associated infection at earlier time points. However, a need exists for a sensitive, reliable, and rapid diagnostic method for detecting the presence of the SARS-associated coronavirus in a biological sample at the earliest possible stage of infection.